Search Results (88)

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory condition of the gastrointestinal tract. It is generally accepted that IBD is characterized by an inappropriate immune response to the intestinal microbiome in genetically susceptible individuals. Despite the available treatment options ranging from salicylates and corticosteroids, to immunosuppressants and biologics, there is still a high unmet medical need for patients who respond poorly to drugs or are not able to tolerate them. Microbiome-based therapeutics offer a valid treatment strategy for IBD with enhanced safety. A butyrate-producing consortium of six commensal strains (MH002) was evaluated in a series of in vitro, ex vivo, and in vivo experiments mimicking multiple IBD-related dysfunctions, namely disrupted intestinal permeability and immune activation. MH002 rapidly produced high levels of butyrate in fed-batch cultures, and significantly increased butyrate levels within one day after administration to IBD-derived gut microbial communities in vitro. Both in Caco-2/peripheral blood mononuclear cells (PBMCs) co-cultures, and IBD patients-derived organoids and colonic explants, MH002 reduced inflammation and restored epithelial barrier integrity. In addition, MH002 promoted wound repair in vitro. Finally, MH002 protected mice and rats from chemically induced colitis. Altogether, results showed that MH002 presents a novel therapeutic avenue for the treatment of IBD. Full article

Executive function (EF) and effortful control (EC) are two similarly defined constructs implicated in self-regulation. Recent debates have questioned whether EF and EC may in fact represent a single construct, and they have undergone scrutiny regarding construct independence. Efforts to differentiate them have further queried whether one may in fact precede the other in early childhood. In a cohort-sequential study of 191 typically developing 4-to-7 year olds (97 girls, 59.7% White), confirmatory factor analysis supported the correlated yet separable two-factor structure of EF and EC with partial scalar invariance across preschool and school-age groups. Longitudinal multi-group modeling was then used to identify predictive pathways between EF, EC, and psychopathology. For both developmental groups, EF predicted externalizing behaviors one year later while EC did not directly predict behavioral outcomes. Internalizing behaviors were found to be highly stable and predictable over time and across age; however, externalizing behaviors significantly predicted internalizing behaviors one year later in the school-age group but not the preschool group. These findings have implications for the measurement of EF and EC in early childhood, as well as the development and prediction of internalizing and externalizing behaviors across the transition to school. Full article

The use of hydrogen as a fuel for piston engines enables environmentally friendly and efficient operation. However, several challenges arise in the combustion process, limiting the development of hydrogen engines. These challenges include abnormal combustion, the high burning velocity of hydrogen-enriched mixtures, increased nitrogen oxide emissions, and others. A rational organization of hydrogen combustion can partially or fully mitigate these issues through the use of advanced methods such as late direct injection, charge stratification, dual injection, jet-guided operation, and others. However, mathematical models describing hydrogen combustion for these methods are still under development, complicating the optimization and refinement of hydrogen engines. Previously, we proposed a mathematical model based on Wiebe functions to describe premixed and diffusion combustion, as well as relatively slow combustion in lean-mixture zones, behind the flame front, and near-wall regions. This study further develops the model by accounting for the combined influence of the mixture composition and engine speed, mixture stratification, and the effects of injection and ignition parameters on premixed and diffusion combustion. Special attention is given to combustion modeling in an engine with single injection and jet-guided operation. Full article

As emission regulations become increasingly stringent, diesel/natural gas dual-fuel engines are regarded as a promising solution and have attracted extensive research attention. However, their complex combustion processes pose significant challenges to traditional combustion modeling approaches. Data-driven modeling methods offer an effective way to capture the complexity of combustion processes, but their performance is critically constrained by the quantity and quality of the test data. To address these limitations, this study proposes a combustion prediction model framework for dual-fuel engines based on neural networks and data augmentation, aiming to achieve high-quality and fast predictions of the heat release rate curve. First, a hybrid regression data augmentation architecture based on an improved Generative Adversarial Network (GAN) is introduced to enable high-quality dataset augmentation. Subsequently, a Bayesian Neural Network (BNN) is employed to construct a Wiebe parameter prediction model for dual-fuel engines with an accelerated and optimized training model. Meanwhile, an adaptive weight allocation method is proposed based on the model’s precision performance, achieving balanced accuracy distribution across multiple output dimensions and further enhancing the model’s generalization ability. Overall, the proposed modeling approach introduces tradeoff optimizations in both data and model dimensions, enhancing the training and learning efficiency, which offers a valuable direction for data-driven prediction models with practical significance. Full article

Nearshore bathymetric data are essential for assessing coastal hazards, studying benthic habitats and for coastal engineering. Traditional bathymetry mapping techniques of ship-sounding and airborne LiDAR are laborious, expensive and not always efficient. Multispectral and hyperspectral remote sensing, in combination with machine learning techniques, are gaining interest. Here, the nearshore bathymetry of southwest Puerto Rico is estimated with multispectral Sentinel-2 and hyperspectral PRISMA imagery using conventional spectral band ratio models and more advanced XGBoost models and convolutional neural networks. The U-Net, trained on 49 Sentinel-2 images, and the 2D-3D CNN, trained on PRISMA imagery, had a Mean Absolute Error (MAE) of approximately 1 m for depths up to 20 m and were superior to band ratio models by ~40%. Problems with underprediction remain for turbid waters. Sentinel-2 showed higher performance than PRISMA up to 20 m (~18% lower MAE), attributed to training with a larger number of images and employing an ensemble prediction, while PRISMA outperformed Sentinel-2 for depths between 25 m and 30 m (~19% lower MAE). Sentinel-2 imagery is recommended over PRISMA imagery for estimating shallow bathymetry given its similar performance, much higher image availability and easier handling. Future studies are recommended to train neural networks with images from various regions to increase generalization and method portability. Models are preferably trained by area-segregated splits to ensure independence between the training and testing set. Using a random train test split for bathymetry is not recommended due to spatial autocorrelation of sea depth, resulting in data leakage. This study demonstrates the high potential of machine learning models for assessing the bathymetry of optically shallow waters using optical satellite imagery. Full article

Manual wheelchair users (MWUs) frequently report shoulder problems and have a three-times-higher likelihood of rotator cuff pathology compared to able-bodied individuals. Shoulder health is crucial for MWU independence, their social participation, and quality of life. Daily activities such as wheelchair propulsion potentially lead to fatigue and overload. Since comprehensive data are limited, this study aimed to implement a wheelchair mobility metrics (WCMM) method to examine various aspects of wheelchair use in daily life. Two inertial measurement units (IMUs) were placed on the wheelchair frame and wheel of 19 participants with a spinal cord injury (SCI). WCMMs like distance covered, number of pushes and turns, and incline were derived from real-life measurements and normalized to a period of 8 h. Large variation was observed among participants. The distance covered ranged from 0.5 to 10.7 km, with the number of pushes from 438 to 4820. The number of turns ranged from 269 to 1396, and the average distance per mobility bout from 5 to 59 m. This wide variation over participants emphasizes the importance of data-driven clinical decision making and patient education. Further studies with larger samples and duration are needed to fully understand MWUs’ mobility patterns and their implications for shoulder health. Full article

As technology continues to reshape education, the integration of peer feedback (PF) is increasingly recognized as a key element in promoting student collaboration and learning. This design study tracks the development and implementation of the Thinq Tank tool, which is aimed at facilitating dialogic PF within computer-supported collaborative-inquiry learning (CSCiL) environments. The research was conducted through three design iterations, comparing two key experimental conditions: one contrasting non-dialogic PF with dialogic PF, and another comparing dialogic PF with scripted dialogic PF featuring dynamic sentence-starters and defined roles. Utilizing a quasi-experimental design, we assessed the overall impact on scientific (collaborative) learning outcomes, students’ perceptions of PF, and the composition and elements of PF dialogues. The findings suggest that the integration of dialogic PF within a CSCiL lesson series helps to boost scientific collaborative learning outcomes and increases student receptivity to PF. The study demonstrates that integrating structured support mechanisms within PF tools promotes PF dialogues in which students critically evaluate each other’s work and collaboratively think about ways to improve quality. These insights illustrate that structured, technology-supported PF can significantly advance inquiry outcomes and foster deeper collaborative learning in secondary STEM education. Full article

Background: The performance of an everolimus-eluting bioresorbable scaffold (BRS) was inferior to an everolimus-eluting metallic drug-eluting stent (DES) with permanent polymer, mainly due the mechanical features of BRS technology. The performance of BRS as compared to metallic DES with bioresorbable polymers remains unstudied. Methods: This prospective, randomized, multicenter, clinical trial enrolled patients who underwent coronary stenting for de novo coronary lesions. Patients were randomly assigned to bioresorbable polymer everolimus-eluting stents (BP-EES) or everolimus-eluting BRS. The primary endpoint was percentage diameter stenosis (in-device) at 6- to 8-month angiographic surveillance. The main secondary endpoint was the device-oriented composite endpoint (DOCE) of cardiac death/target vessel-myocardial infarction/target lesion revascularization assessed after 12 months and 5 years. Results: The trial was prematurely terminated after the enrollment of 117 of 230 patients (BP-EES, n = 60; BRS, n = 57) due to safety issues associated with BRS technology. The primary endpoint of in-device diameter stenosis at angiographic surveillance was 12.5 ± 7.7% with BP-EES versus 19.3 ± 16.5% with BRS (p = 0.01). The DOCE occurred in 5.0% in the BP-EES group versus 12.3% of patients in the BRS group (hazard ratio [HR] 2.48, 95% confidence interval [CI] 0.64–9.58, p = 0.19) after 12 months and in 11.7% in the BP-EES group versus 26.4% of patients in the BRS group (HR 2.38, 95% CI 0.97–5.84, p = 0.06) after 5 years. Conclusions: BP-EES showed superior mid-term angiographic performance compared with BRS. Clinical event rates did not differ significantly between the groups up to 5 years of follow-up. These results should be interpreted with caution in view of the premature discontinuation of the study. Full article

Cellulose, a sustainable raw material, holds great promise as an ideal candidate for membrane materials. In this work, we focused on establishing a low-cost route for producing cellulose microfiltration membranes by adopting a co-solvent system comprising the ionic liquid 1-ethyl-3-methylimidazolium acetate ([EMIM]OAc) and acetone. The introduction of acetone as a co-solvent into the casting solution allowed control over the viscosity, thereby significantly enhancing the morphologies and filtration performances of the resulting cellulose membranes. Indeed, applying this co-solvent allowed the water permeability to be significantly increased, while maintaining high rejections. Furthermore, the prepared cellulose membrane demonstrated excellent fouling resistance behavior and flux recovery behavior during a challenging oil-in-water emulsion filtration. These results highlight a promising approach to fabricate high-performance cellulose membranes. Full article

Background: Sarcopenia is associated with adverse health outcomes. Understanding the association between sarcopenia, multidimensional frailty, and prognosis is essential for improving patient care. The aim of this study was to assess the prevalence and prognostic signature of sarcopenia in an acute hospital setting co-led by internists and geriatricians. Methods: Sarcopenia was assessed by applying the European Working Group on Sarcopenia in Older People (EWGSOP2) algorithm, including the SARC-F score, handgrip strength, bioelectrical impedance analysis (BIA), and Timed Up and Go (TUG) test, to 97 older multimorbid inpatients (76.5 ± 6.8 years, 55% women). The patients underwent a Comprehensive Geriatric Assessment (CGA) including an evaluation of Geriatric Syndromes (GSs) and Resources (GR) and prognosis calculation using the CGA-based Multidimensional Prognostic Index (MPI), European Quality of life—5 Dimensions (EQ-5D-5L) scale, Rosenberg Self-Esteem Scale (RSES), and Geriatric Depression Scale (GDS). Information on survival and rehospitalizations was collected 1, 3, and 6 months after discharge. Results: Sarcopenia was present in 63% (95% CI: 54–72%) of patients and categorized as probable (31%), confirmed (13%), and severe sarcopenia (18%). Sarcopenic patients showed significantly higher median MPI-values (p < 0.001), more GSs (p = 0.033), fewer GR (p = 0.003), lower EQ-5D-5L scores (p < 0.001), and lower RSES scores (p = 0.025) than non-sarcopenic patients. Six months after discharge, being sarcopenic at baseline was predictive of falls (p = 0.027) and quality of life (p = 0.043), independent of age, gender, and MPI. Conclusions: Sarcopenia is highly prevalent in older hospitalized multimorbid patients and is associated with poorer prognosis, mood, and quality of life up to 6 months after discharge, independent of age, sex, and MPI as surrogate markers of biological age. Full article

The COVID-19 pandemic has resulted in lasting effects on children, necessitating a thorough understanding of its impact for effective recovery planning. This study investigated the associations among COVID-19 family stress, family functioning, children’s lifestyle behaviors (i.e., healthy food intake, unhealthy food intake, physical activity, and screen time), and their health-related quality of life (HRQOL). Data from a 2022 survey of parents with children aged 5 to 12 (mean age of boys: 8.36, mean age of girls: 7.76) in the United States through the online Prolific platform were analyzed using path analysis and gender-based multi-group analysis. The results showed an inverse relationship between family stressors and functioning (β = −0.39, p < 0.05). COVID-19 family stress was negatively related to child physical HRQOL (β = −0.20, p < 0.05) but not psychosocial HRQOL. Family functioning showed a positive relation with child healthy food intake (β = 0.26, p < 0.05) and a negative relation with unhealthy diet consumption (β = −0.27, p < 0.05), while no significant associations were found with child physical activity and screen time. Family functioning was indirectly associated with both types of HRQOL through the child’s eating patterns. These relationships were more pronounced for girls. The findings point to a complex interplay between family stress and functioning, dietary habits, and the HRQOL of children during the COVID-19 pandemic, particularly concerning girls’ food intake and well-being. Full article

Most antiviral and anticancer nucleosides are prodrugs that require stepwise phosphorylation to their triphosphate nucleotide form for biological activity. Monophosphorylation may be rate-limiting, and the nucleotides may be unstable and poorly internalized by target cells. Effective targeting and delivery systems for nucleoside drugs, including oligonucleotides used in molecular therapeutics, could augment their efficacy. The development of a carrier designed to effect selective transmembrane internalization of nucleotides via the asialoglycoprotein receptor (ASGPr) is now reported. In this work, the polycationic, polygalactosyl drug delivery carrier heptakis[6-amino-6-deoxy-2-O-(3-(1-thio-β-D-galactopyranosyl)-propyl)]-β-cyclodextrin hepta-acetate salt (GCyDAc), potentially a bifunctional carrier of (poly)nucleotides, was modeled by molecular docking in silico as an ASGPr-ligand, then synthesized for testing. The antivirals arabinosyl adenine (araA, vidarabine, an early generation antiviral nucleoside), arabinosyl adenine 5′-monophosphate (araAMP), and 12-mer-araAMP (p-araAMP) were selected for individual formulation with GCyDAc to develop this concept. Experimentally, beta cyclodextrin was decorated with seven protonated amino substituents on the primary face, and seven thiogalactose residues on its secondary face. AraA, araAMP, and p-araAMP were individually complexed with GCyDAc and complex formation for each drug was confirmed by differential scanning calorimetry (DSC). Finally, the free drugs and their GCyDAc complexes were evaluated for antiviral activity using ASGPr-expressing HepAD38 cells in cell culture. In this model, araA, araAMP, and p-araAMP showed relative antiviral potencies of 1.0, 1.1, and 1.2, respectively. In comparison, GCyDAc-complexes of araA, araAMP, and p-araAMP were 2.5, 1.3, and 1.2 times more effective than non-complexed araA in suppressing viral DNA production. The antiviral potencies of these complexes were minimally supportive of the hypothesis that ASGPr-targeted, CyD-based charge-association complexation of nucleosides and nucleotides could effectively enhance antiviral efficacy. GCyDAc was non-toxic to mammalian cells in cell culture, as determined using the MTS proliferation assay. Full article

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on sensory neurons and immune cells. We hypothesize that TRPV1 plays a role in human eosinophil function and is modulated by inflammatory conditions. TRPV1 expression on human eosinophils was examined by qPCR, flow cytometry, and immunohistochemistry, respectively. TRPV1 functionality was analyzed by investigating calcium flux, apoptosis, modulation by cytokines and acidic pH, and CD69 externalization using flow cytometry. Activation of TRPV1 induced calcium influx and prolonged survival. Although eosinophils were not directly activated by TRPV1 agonists, activation by IL-3 or GM-CSF was mainly restricted to TRPV1-positive eosinophils. TRPV1 surface content was increased by acidic pH, IL-3, IL-31, IL-33, TSLP, TNF-α, BDNF, and NGF-β. Interestingly, TRPV1 was also expressed by eosinophils located in proximity to peripheral nerves in atopic dermatitis (AD) skin. In conclusion, eosinophils express functional TRPV1 channels which are increased by extracellular acidification and AD-related cytokines. Since eosinophils also express TRPV1 in AD skin, our results indicate an important role of TRPV1 for neuroimmune interaction mechanisms in itchy, inflammatory skin diseases, like AD. Full article

Electrospun nanofiber mats have a high specific surface area and very small pores which can be tailored by the spinning process. They are thus highly suitable as filters for small particles and molecules, such as organic dyes. On the other hand, they are usually very thin and thus have low mechanical properties. As a potential reinforcement, mycelium of Pleurotus ostreatus was grown on poly(acrylonitrile) nanofiber mats and thermally solidified after fully covering the nanofiber mats. This study investigates whether the filtration efficiency of the nanofiber mats is altered by the mycelium growing through it and whether the mechanical properties of the nanofibrous filters can be improved in this way. The study shows fast and reliable growth of the mycelium on the nanofiber mats and high filtration efficiency for astra blue and chlorophyll, while indigo carmine showed only very low filtration efficiency of up to 20%. For chlorophyll and safranin, membranes with mycelium showed higher filtration than pure nanofiber mats. In diffusion cell tests, especially astra blue was strongly adsorbed on the membranes with mycelium. Full article

Daily wheelchair ambulation is seen as a risk factor for shoulder problems, which are prevalent in manual wheelchair users. To examine the long-term effect of shoulder load from daily wheelchair ambulation on shoulder problems, quantification is required in real-life settings. In this study, we describe and validate a comprehensive and unobtrusive methodology to derive clinically relevant wheelchair mobility metrics (WCMMs) from inertial measurement systems (IMUs) placed on the wheelchair frame and wheel in real-life settings. The set of WCMMs includes distance covered by the wheelchair, linear velocity of the wheelchair, number and duration of pushes, number and magnitude of turns and inclination of the wheelchair when on a slope. Data are collected from ten able-bodied participants, trained in wheelchair-related activities, who followed a 40 min course over the campus. The IMU-derived WCMMs are validated against accepted reference methods such as Smartwheel and video analysis. Intraclass correlation (ICC) is applied to test the reliability of the IMU method. IMU-derived push duration appeared to be less comparable with Smartwheel estimates, as it measures the effect of all energy applied to the wheelchair (including thorax and upper extremity movements), whereas the Smartwheel only measures forces and torques applied by the hand at the rim. All other WCMMs can be reliably estimated from real-life IMU data, with small errors and high ICCs, which opens the way to further examine real-life behavior in wheelchair ambulation with respect to shoulder loading. Moreover, WCMMs can be applied to other applications, including health tracking for individual interest or in therapy settings. Full article